Follistatin treatment suppresses SERCA1b levels independently of other players of calcium homeostasis in C2C12 myotubes

Fodor, János and Gomba-Tóth, Adrienn and Oláh, Tamás and Almássy, János and Zádor, Ernő and Csernoch, László (2017) Follistatin treatment suppresses SERCA1b levels independently of other players of calcium homeostasis in C2C12 myotubes. JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY, 38 (2). pp. 215-229. ISSN 0142-4319

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Abstract

Follistatin (FS) is a high affinity activin-binding protein, neutralizing the effects of the Transforming Growth Factor-beta (TGF-beta) superfamily members, as myostatin (MSTN). Since MSTN emerged as a negative regulator, FS has been considered as a stimulator of skeletal muscle growth and differentiation. Here, we studied the effect of FS administration on the Ca2+-homeostasis of differentiating C2C12 skeletal muscle cells. FS-treatment increased the fusion index, the size of terminally differentiated myotubes, and transiently elevated the expression of the calcium-dependent protein phosphatase, calcineurin, at the beginning of differentiation. Functional experiments did not detect any alterations in the Ca2+ transients following the stimulation by KCl or caffeine in myotubes. On the other hand, decreased Ca2+-uptake capability was determined by calculating the maximal pump rate (332 +/- 17 vs. 279 +/- 11 A mu M/s, in control and FS-treated myotubes, respectively; p < 0.05). In the same way, the expression and ATPase activity of the neonatal sarcoplasmic/endoplasmic reticulum Ca(2+)ATPase (SERCA1b) were decreased (0.59 +/- 0.01 vs. 0.19 +/- 0.01 mM ATP/min, in control and FS-treated myotubes, respectively; p < 0.05). However, the expression level of other proteins involved in Ca2+-homeostasis and differentiation (calsequestrin, STIM1, MyoD) were not affected. Our results suggest that the FS controlled myotube growth is paralleled with the tight regulation of cytosolic calcium concentration, and the decline of SERCA1b appears to be one of the key components in this process.

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